DHEA therapy for the aging immune system

From the desk of our founder, Dr. Ron Brown:

True Balance has been involved in the provision of Bioidentical Hormone Replacement Therapy (BHRT) treatment programs since 2007. Due to the large number of patients that we have treated, True Balance is to my knowledge the largest BHRT clinic in Canada. Over these years we have accumulated a very significant amount of experience as it relates to hormone treatment of women and men over the age of 50. We have all come to learn that people over the age of 60 are especially susceptible to the complications of infections. It has been known for many years, that as we age, our immune system function deteriorates. This decline in immune function has been termed ‘immunosenescence’(1).

While medical science has known about this decline in immune function for many years, the underlying causes are not clearly known. There are several very clear changes that happen: (2,3)

• Decreased white blood cell (neutrophil) function.

• Decreased natural killer (NK) function.

• Thymus atrophy

• Decreased naïve T-cell numbers.

Over the years, an association has been drawn between declining hormone levels and immune function. A term called ‘endocrinesenescence' has been coined for this association (7,8). As we age, the hypothalamic-pituitary (HPA) axis in the brain, undergoes several changes and becomes chronically over-activated. This HPA over-activation, which is in part due to declining sex hormone levels, leads to a reduced ability to fight viral infectious diseases such as influenza. As well, DHEA production declines by up to 90% from the levels seen in young healthy people. In fact, lab reference ranges are ‘adjusted’ for age to make this seem like normal! DHEA is a hormone produced by the adrenal glands and higher levels are linked to improved quality of life. DHEA is the natural balancing hormone that counter balances the negative effects of cortisol in the body. As we age, cortisol levels increase and this rise has negative effects on the immune system. These changes in DHEA and cortisol seen with the aging process lead to an elevated cortisol/DHEA ratio. This altered ratio interferes with immune function by reducing the CD+4-CD+8 ratio of T-helper cells (4,5,6,9). The net effect is an inability to clear viral infections, particularly in the elderly. As well, DHEA has been shown to improve the Th1 side of the immune response, which is particularly important in fighting viral infections (13). There is also evidence that adding zinc to DHEA supplementation boosts the Th1 sideof the immune system(12).

At True Balance, we have used DHEA as an integral part of our BHRT program since its inception. While the evidence is scant, there is in fact human evidence of an improvement in immune function in men over the age of 60 with DHEA. Khorran et al (10) treated men with 50 mg of DHEA. They observed a 20% increase in IGF-1, which is a surrogate marker of human growth hormone. There was also a significant activation of the immune function, with a 40% increase in T cell activation. T cells are the arm of the immune system involved in protecting us from viral infections. There are a number of valid scientific articles that show improved immune function with supplemental DHEA.

In summary, as we age our natural production of DHEA declines. Parallel to this, we experience a decline in our immune system function and its ability to fight viral infections. While association does not prove causation, the observed improvement in immune function with DHEA supplementation is scientifically intriguing. One could argue that since DHEA is available over the counter in the USA, there is no desire for DHEA research in the pharmaceutical community. Conspiracy theorists would cite this as a reason for the lack of scientific interest and studies. I am not of this opinion and believe economic factors explain the lack of sponsored studies. With a significant part of the population ‘at risk’, we do not have the benefit of time to research this area. I have seen no suggestions of treatment programs to reduce risk of coronavirus infection or complications of infection. In the absence of better alternatives, I feel compelled to bring the potential benefits of DHEA supplementation to light.

I believe in the context of a global viral pandemic, DHEA supplementation should be considered in ‘at risk’ individuals. Those individuals would be persons 60 years of age or older, especially if they have underlying metabolic or respiratory diseases. I also believe DHEA should be administered in the context of a complete BHRT program which offers testing, appropriate dosing and proper follow up.

Further study of DHEA must be done. If corporate interests see no utility to this medication, government should step in to sponsor proper scientific studies in the future. As well, Health Canada should be held responsible for their decision to label DHEA as an anabolic hormone that requires a medical prescription. I would ask, why in the USA, is this naturally produced compound sold in grocery stores if it is in fact 'dangerous'? Health Canada should review and amend its designation for DHEA when this pandemic crisis passes.

Sincerely Yours,

Dr. R. J. Brown

References

1. Bauer, M. E. (2005). Stress, glucocorticoids and ageing of the immune system. Stress, 8(1), 69-83.2.

2. Phillips, A. C., Burns, V. E., & Lord, J. M. (2007). Stress and exercise: Getting the balance right for aging immunity. Exercise and sport sciences reviews, 35(1), 35-39.

3. Hawkley, L. C., & Cacioppo, J. T. (2004). Stress and the aging immune system. Brain, behavior, and immunity, 18(2), 114-119.

4. Butcher, S. K., Killampalli, V., Lascelles, D., Wang, K., Alpar, E. K., & Lord, J. M. (2005). Raised cortisol: DHEAS ratios in the elderly after injury: potential impact upon neutrophil function and immunity. Aging cell, 4(6), 319-324.

5. De Martinis, M., Franceschi, C., Monti, D., & Ginaldi, L. (2007). Apoptosis remodeling in immunosenescence: implications for strategies to delay ageing. Current medicinal chemistry, 14(13), 1389-1397.

6. Schmidt, M., Naumann, H., Weidler, C., Schellenberg, M., Anders, S., & Straub, R. H. (2006). Inflammation and sex hormone metabolism. Annals of the New York Academy of Sciences, 1069, 236–246. https://doi.org/10.1196/annals.1351.021

7. Corsini, E., Galbiati, V., Papale, A., Kummer, E., Pinto, A., Serafini, M. M., Guaita, A., Spezzano, R., Caruso, D., Marinovich, M., & Racchi, M. (2016). Role of androgens in dhea-induced rack1 expression and cytokine modulation in monocytes. Immunity & ageing : I & A, 13, 20. https://doi.org/10.1186/s12979-016-0075-y

8. Endocrine Aspects 2009; 19: 313

9. Applied Physiology 2008; 33(3) Buford et al

10. Khorram, O., Vu, L., & Yen, S. S. (1997). Activation of immune function by dehydroepiandrosterone (DHEA) in age-advanced men. The journals of gerontology. Series A, Biological sciences and medical sciences, 52(1), M1–M7. https://doi.org/10.1093/gerona/52a.1.m111. Proc Soc Exp Biol Med 1999; Sep 221(4) 326-35 Catalina et al

12. Immunobiology 2010; 215(5): 427-34 Brazco et al

13. Kanda, N., Hoashi, T., & Saeki, H. (2019). The Roles of Sex Hormones in the Course of Atopic Dermatitis. International journal of molecular sciences, 20(19), 4660. https://doi.org/10.3390/ijms20194660